Method for measuring blood flow

ABSTRACT

A technique for determining blood flow in a living body by changing the thermal energy level by a predetermined amount at a site in a blood flow path and detecting temperatures at locations upstream and downstream of the site. The temperature difference at such locations is determined and the blood flow is calculated as a function of the change in energy level and of the temperature differences measured prior to and following the change in energy level.

INTRODUCTION

[0001] This invention relates generally to techniques for measuringblood flow in a body and, more particularly, to the use preferably ofone or more temperature sensors for measuring thermal energy changes inthe blood flowing through the heart and to the use of unique dataprocessing techniques in response thereto for determining cardiacoutput.

BACKGROUND OF THE INVENTION

[0002] While the invention can be used generally to measure blood flowat various locations in a body, it is particularly useful in measuringblood flow in the heart so as to permit the measurement of cardiacoutput. Many techniques for measuring cardiac output have been suggestedin the art. Exemplary thermodilution techniques described in thetechnical and patent literature include: “A Continuous Cardiac OutputComputer Based On Thermodilution Principles”, Normann et al., Annals ofBiomedical Engineering, Vol. 17, 1989; “Thermodilution Cardiac OutputDetermination With A single Flow-Directed Catheter”, Forrester, et al.,American Heart Journal, Vol. 83, No. 3, 1972; “Understanding Techniquesfor Measuring Cardiac Output”, Taylor, et al., BiomedicalInstrumentation & Technology, May/June 1990; U.S. Pat. Nos. 4,507,974 ofM. L. Yelderman, issued Apr. 2, 1985; 4,785,823, of Eggers et al.,issued on Nov. 22, 1988; and 5,000,190, of John H. Petre, issued on Mar.19, 1991.

[0003] A principal limitation in the quanification of cardiac output isthe existence of thermal fluctuations inherent in the bloodstream.Previous methods work with those fluctuations while observing theeffects of an input signal to calculate cardiac output. The inventiondescribed herein uses a differential measurement technique tosubstantially eliminate the effect of the thermal fluctuations,permitting the use of a minimal thermal input signal, which allowsfrequent or continuous measurements.

[0004] It is desirable to obtain accurate cardiac output measurements inan effectively continuous manner, i.e., several times a minute, so thata diagnosis can be achieved more rapidly and so that rapid changes in apatient's condition can be monitored on a more continuous basis than ispossible using current techniques. Moreover, it is desirable to obtaininstantaneous measurements of the cardiac output on a beat-to-beat basisto evaluate the relative changes which occur from beat to beat, as wellas to determine the presence of regurgitation.

BRIEF SUMMARY OF THE INVENTION

[0005] In accordance with general principal of the invention, blood flowand/or cardiac output is determined rapidly, using a technique by whichan indicator substance, or agent, is introduced into the bloodstreambetween a pair of detectors. The detectors are sensitive to a parameterfunctionally related to the concentration or magnitude in thebloodstream of the selected indicator agent. The detectors arepositioned apart by a distance functionally sufficient to allow ameasurement to be made of the differential value of the selectedparameter as it exists from time-to-time between the two detectors. Theindicator agent, for example, may be a substance to change the pH of theblood, a fluid bolus carrying thermal energy, or a substance to change aselected characteristic of the blood, or the direct introduction ofthermal energy, or the like.

[0006] A determination is made of the difference in the values of theselected blood parameter as it exists at the two detectors, prior to theintroduction of indicator agent (i.e., the first differential value).The selected indicator agent is then introduced in a predeterminedmagnitude. Then again a determination is made of the difference invalues of the selected parameter as it exists at the locations of thetwo detectors (i.e., the second differential value).

[0007] Blood flow or cardiac output, depending on the specific locationof the detectors, can then be determined as a function of the differencebetween the first differential value and the second differential value.Because the ultimate measurement of blood flow or cardiac output isbased on the difference of the differences, the system operateseffectively with the introduction of the indicator agent in a very lowmagnitude. In turn, this allows measurements to be made rapidly so thateffectively continuous measurements are obtained.

[0008] In accordance with a preferred embodiment of the invention, forexample, cardiac output can be determined rapidly and with low levels ofthermal energy input. To achieve such operation, in a preferredembodiment, the technique of the invention uses a pair of temperaturesensors positioned at two selected locations within a catheter which hasbeen inserted into the path of the blood flowing through the heart of aliving body. The sensors detect the temperature difference between thetwo locations. Depending on the location of the temperature sensors inthe circulatory system, the measured temperature difference varies overtime. It has been observed that when the temperature sensors are placedwithin the heart, e.g., so that one sensor lies in the vena cava, forexample, and the second in the right ventricle or pulmonary artery, thetemperature difference varies in a synchronous manner with therespiratory cycle.

[0009] Thus, in the preferred embodiment of the invention thetemperature difference over at least one respiratory cycle is measuredand averaged to provide an average temperature difference. Theaveraging, or integrating, action effectively eliminates, as aconfounding factor in the determination of cardiac output, the effect ofinstantaneous blood temperature fluctuations, such as cyclical,respiratory-induced fluctuations.

[0010] To make such determinations, an average temperature difference isfirst calculated over a time period of at least one respiratory cycle inwhich no thermal energy is introduced into the blood flow path. Thermalenergy of a predetermined and relatively low magnitude is thenintroduced into the blood flow path to produce a heating action thereinat a location between the two temperature sensors. Once the temperaturerise induced by the heating stabilizes, the average temperaturedifference between the two locations is again calculated fromtemperature difference measurements over a time period of at least onerespiratory cycle at the higher temperature level. The differencebetween the average temperature differences which occurs when thethermal energy is turned on, referred to as the rising temperaturechange, is determined. The difference between the average temperaturedifferences which occurs when the thermal energy is turned off, referredto as the falling temperature change, is similarly determined. Thecardiac output is calculated as a function of the thermal energy inputand the rising and falling temperature changes. Because a relatively lowlevel of thermal energy is used in making measurements, the overallsequence of determinations can be safely repeated multiple times perminute, for example, so that an effectively continuous, orquasi-continuous, determination of cardiac output is obtained.

[0011] In accordance with a further embodiment of the invention, atemperature sensor that also acts as a source of thermal energy, e.g., athermistor, is positioned at a third location in the cardiac blood flowpath. Power is supplied to the sensor sufficient to elevate thetemperature of the sensor from a first temperature level to a secondtemperature level. In one embodiment of the invention, the temperatureof the sensor is changed from the first to the second level and ismaintained constant at said second level by varying the power that issupplied thereto. Such varying power is proportional to theinstantaneous flow velocity and, hence, assuming a constant flow area,is proportional to the instantaneous cardiac output. Measurement of thesensor heating power and the temperature increment at the sensor canthus be used to continuously effect a determination of the instantaneouscardiac output. Further, for example, when the sensor is placeddownstream at the outlet of one of the heart chambers, the variation inflow output over the cardiac cycle can be analyzed to provide anindication of the regurgitation characteristics of the heart outletvalve over the cardiac cycle. Moreover, such instantaneous cardiacoutput determination can be further refined to compensate orfluctuations in the temperature of the blood flowing through the heartby measuring the instantaneous temperature of the blood with anothertemperature sensor at a nearby location and appropriately taking intoaccount such temperature variations when determining the cardiac output.

[0012] In another application, both the continuous cardiac outputdeterminations and the instantaneous cardiac output determinations, asdescribed above, can be combined. Thus, three temperature sensors and asource of thermal energy can all be used in combination tosimultaneously provide an accurate and effectively continuousdetermination of time-averaged cardiac output, and a determination ofinstantaneous cardiac output at each instant of the cardiac cycle. Instill another application, two temperature sensors and a source ofthermal energy can be used in an appropriate sequence to provide theaveraged cardiac output determination and the instantaneous cardiacoutput determination.

DESCRIPTION OF THE INVENTION

[0013] The invention can be described in more detail with the help ofthe accompanying drawings wherein

[0014]FIG. 1 shows a simplified diagrammatic view of a human heart;

[0015]FIG. 2 shows a simplified diagrammatic view of a catheter usefulin the invention;

[0016]FIG. 3 shows a flow chart depicting steps in a process used in theinvention;

[0017]FIG. 3A shows a smooth temperature difference curve obtained inthe process depicted in FIG. 3;

[0018]FIG. 4 shows a flow chart depicting steps in another process usedin the invention;

[0019]FIG. 5 shows a flow chart depicting steps in still another processof the invention;

[0020]FIG. 6 shows a graph depicting a temperature/time relation used inthe invention;

[0021]FIG. 7A shows a simplified diagrammatic view of another catheterused in the invention;

[0022]FIG. 7B shows a flow chart depicting steps in still anotherprocess of the invention;

[0023]FIGS. 8A, 8B, and 8C show flow charts depicting still otherprocesses of the invention;

[0024]FIGS. 9A, 9B, and 9C show graphs of parameter relationships usedin the invention; and

[0025]FIG. 10 shows a graph useful for calibrating the flow values for acatheter used in the invention.

[0026] As can be seen in FIG. 1, which represents a human heart 10 in amuch simplified diagrammatic form, a flexible catheter 11 is insertedthrough the veins into the right atrium, or auricle, 12 of the heartand, thence, through the right ventricle 13 until the end of thecatheter resides in or near the exit, or pulmonary, artery 14 whichleads to the lungs. As is well known, blood flows (as represented by thearrows) from the input vein 15, i.e., the vena cava, into the rightatrium and right ventricle and thence outwardly to the lungs andsubsequently returns from the lungs into the left atrium 16, through theleft ventricle 17 and thence outwardly into the aorta 18.

[0027] In accordance with the embodiment of the invention, shown withreference to FIG. 1, temperature sensors, e.g., thermistors, are carriedby the catheter so that, when inserted as shown in FIG. 1, a firstsensor 19 is positioned at a location within the vena cava 15 or rightatrium 12 and a second sensor 20 is positioned at a location in or nearthe pulmonary artery 14.

[0028] For simplicity, the flexible catheter 11 is depicted in FIG. 2 inan extended condition with temperature sensors 19 and 20 at twodifferent locations for measuring temperatures T₁ and T₂, respectively.A power source 21 of thermal energy which is borne, or carried, by thecatheter 11 is positioned in the right atrium at a location betweensensors 19 and 20. In a particular embodiment, the catheter-borne sourceis, for example, a coil of resistive wire placed on or embedded in thesurface of catheter 11, to which an AC or a DC voltage (not shown) at acontrollable level is supplied so as to generate thermal energy, i.e.heat. The magnitude of the thermal energy can be suitably controlled toinsert a predetermined amount of thermal energy at a selected time,which thermal energy is transferred to the blood flowing through theheart so as to raise its temperature. The energy source is positioned ata sufficient distance from the sensor 19 that the latter is effectivelythermally isolated from the site of the thermal energy source.

[0029] While the locations of the sensors 19 and 20 and the energysource 21 can be as shown in FIG. 1, alternative locations can also beused. Thus, the sensor 19 can be positioned in the vena cava 15, whilethe energy source 21 is located in the right atrium 12 and the sensor 20in either the right atrium or the right ventricle. Moreover, if sensor19 is positioned in the vena cava 15, the entire energy source 21, whichis normally elongated, need not be located in the right atrium and canhave a portion thereof in the vena cava and a portion thereof in theright atrium. Such source should preferably be at least partiallylocated in the right atrium. Further, sensor 20 may be positioned in theright ventricle near the pulmonary artery 14 or may be located in thepulmonary artery itself at or near the right ventricle.

[0030] The temperatures T₁ and T₂ at locations 19 and 20 upstream anddownstream, respectively, from the thermal energy source 21 aremonitored and processed appropriately by a digital microprocessor. Inaccordance with the invention, the instantaneous temperatures areobtained as the outputs T₁(t) and T₂(t) of the temperature sensors 19and 20, respectively. The outputs are connected to a differentialamplifier to generate an analog signal which is proportional to thetemperature difference ΔT(t)=T₁(t)−T₂(t) between them. The temperaturedifference signal ΔT(t) is digitized and sampled at selected timeintervals by an analog-to-digital/sampling circuit. The digitizedsampled temperature difference values and the known thermal energyvalues are supplied to a digital microprocessor which then suitablyprocesses the data to provide the desired cardiac output information.The processing stages used in the host microprocessor are implemented bysuitable programming of the microprocessor and are discussed below withthe help of FIGS. 3-6.

[0031] The source 21 of thermal energy is alternately turned on and off.If it is assumed that thermal stability is reached after each change andthat there is a substantially constant rate of blood flow, a stabletemperature difference can be measured in each case. The quantity ofblood flowing past the thermal energy source, i.e., the cardiac output,can be derived from such temperature difference measurements. However,such derivation is complicated by two factors which may affect themeasurement of blood flow. First, the rate of blood flow through theheart is not substantially constant but surges with each heartcontraction. Second, the temperature of the blood flowing through theheart is not constant but varies with each respiratory (breathing)cycle. In a preferred embodiment, the processing of the data takes suchfactors into account, as discussed below.

[0032] The process for determining cardiac output is performed in amicroprocessor 2 which in a first embodiment is programmed to respond tothe temperatures sensed at T₁ and T₂ and to perform the steps depictedin accordance with the flow charts shown in FIGS. 3-5. From a knowledgeof such flow charts, it would be well within the skill of those in theart to appropriately program any suitable and known digitalmicroprocessor, such as a personal computer, to perform the steps shown.

[0033]FIG. 3 depicts a basic process, identified as Process I, which isused in the overall processing of temperature data for determiningcardiac output, as subsequently depicted in FIGS. 4 and 5. In the basicprocess shown in FIG. 3, a temperature difference as a function of timeΔT(t) is determined by a differential amplifier which responds to T₁(t)and T₂(t). Such differences may be effectively smoothed, or filtered, toproduce a smooth temperature difference curve, as shown in FIG. 3A,which varies as a function of time in a cyclic manner which dependsprincipally on the respiratory cycle of the person whose cardiac outputis being determined.

[0034] The periods π₁, π₂ . . . π_(n) for each respiratory cycle aredetermined over n cycles. A characteristic of the temperature differenceat each cycle is determined. For example, such characteristic preferablyis the averaged temperature difference during each cycle (ΔT_(π1),ΔT_(π2) . . . ΔT_(π2) . . . ΔT_(πn)). (Alternatively, for example, thepeak temperature differences may be the determined characteristic.)These averaged temperature differences (ΔT_(πn)) are added for the ncycles involved and are divided by n to determine an averagedtemperature difference per cycle (ΔT_(πn)). The use of Process I isdepicted in the process steps shown in FIG. 4, identified as Process II.

[0035] As seen therein, the steps of Process I are first performed whenthe source 21 of thermal energy (i.e., a heater) is turned off and theaverage {overscore (ΔT)}_(off) value per cycle is determined andsuitably stored. The sampling time at which such determination is madeis depicted in FIG. 6 as the sample time period S1.

[0036] The heater 21 is then turned on for a specific time period tosupply a known amount of power P to the blood flowing through the heartand, accordingly, the temperature of the blood flowing past the heaterrises and the temperature difference ΔT(t) rises over a transition, ordelay, rise time period, t_(R1), shown in FIG. 6 and designated as D1,after which the temperature difference generally stabilizes over asecond sample time period S2. As seen in FIG. 4, after the heater 21 isturned on and the temperature has stabilized, Process I is performed,again over n cycles, e.g., over the time period S2, and the averagedtemperature difference {overscore (ΔT)}_(on) is determined with theheater turned on and is suitably stored. The heater is then turned offand the temperature falls over a transition, or delay, fall time periodt_(F1,) shown in FIG. 6 and designated as D2, generally to its formervalue.

[0037] Cardiac output is calculated using the averaged temperaturedifferences when the energy is off and the averaged temperaturedifferences when the energy is on, by the relationship: $\begin{matrix}{{F = \frac{P}{C_{P}\left( {{\overset{\_}{\Delta \quad T}}_{on} - {\overset{\_}{\Delta \quad T}}_{off}} \right)}}\quad} \\{{{where}:F} = {Flow}} \\{P = {Power}} \\{C_{P} = {{heat}\quad {capacitance}}} \\{{{\overset{\_}{\Delta \quad T}}_{on} = {{average}\quad {temperature}\quad {for}\quad {power}\quad {on}}}\quad} \\{{\overset{\_}{\Delta \quad T}}_{off} = {{average}\quad {temperature}\quad {for}\quad {power}\quad {off}}}\end{matrix}$

[0038] As seen in FIG. 5, the steps of Process II are repeatedindefinitely for N data collection cycles, a data collection cycle beingdesignated as including the time periods S1, D1, S2, and D2, as shown inFIG. 6. For each data collection cycle the rise time temperaturedifference ΔT_(R) between the averaged temperature difference {overscore(ΔT)}_(on) at S2 and the averaged temperature difference {overscore(ΔT)}_(off) at S1 and the fall time temperature difference ΔT_(F)between the averaged temperature difference {overscore (ΔT)}_(off) at S1and the averaged temperature difference {overscore (ΔT)}_(on) at S2 aredetermined.

[0039] The flow, F_(R,) is calculated for each data collection cyclefrom the known amount of power P introduced into the blood flow streamby the energy source, or heater 21, from the known heat capacitance ofblood, C_(P,) and from the difference in the averaged temperaturedifferences {overscore (ΔT)}_(on) and {overscore (ΔT)}_(off), whichoccurs over the data collection cycle S1+D1+S2 in accordance with thefollowing relationship:${F_{R} = \frac{P}{C_{P}\left( {{\overset{\_}{\Delta \quad T}}_{on} - {\overset{\_}{\Delta \quad T}}_{off}} \right)}}\quad$

[0040] In a similar manner, the flow F_(F) is calculated from P, C_(P)and the difference in the averaged temperature differences ΔT_(on) andΔT_(off) which occurs over the later portion of the data collectioncycle S1+D1+S2 in accordance with the following relationship:${F_{F} = \frac{P}{C_{P}\left( {{\overset{\_}{\Delta \quad T}}_{on} - {\overset{\_}{\Delta \quad T}}_{off}} \right)}}\quad$

[0041] F_(R) and F_(F) can be averaged to obtain the averaged flow({overscore (F)}) over one data collection cycle as shown in FIG. 6.$\overset{\_}{F} = \frac{F_{R} + F_{F}}{2}$

[0042] A suitable calibration constant can be used to adjust the valuesof F_(R), F_(F) and {overscore (F)}.

[0043] Accordingly, by using two temperature sensors 19 and 20, cardiacoutput can be determined several times a minute in accordance with FIGS.3-6, yielding an effectively continuous cardiac output value. Becausesuch measurements can be made using relatively low power levels, thedanger that the heart may be damaged by the introduction of thermalenergy is substantially eliminated.

[0044] It will be apparent that the foregoing technique, which has beendescribed in connection with the direct introduction of heat as anindicator agent and the measurement of temperature, can readily beperformed by those skilled in the art by using indicator agents whichaffect the pH of the blood or change other blood parameters.

[0045] In some situations it may be desirable to provide more frequentindications of cardiac output, such as, for example, the instantaneouscardiac output or the cardiac output averaged over each individualcardiac cycle (i.e. each heart beat). Such information can be providedusing the further embodiments of the invention discussed below withreference to FIGS. 7-8. A single temperature sensor 30 at a locationnear the distal end of the catheter 31 (as shown in FIG. 7A) can be usedto determine the instantaneous or beat-to-beat blood velocity V(t). Theblood velocity can be combined with the cardiac output averaged over oneor more data collection cycles to calculate instantaneous cardiacoutput. The process used is shown in the process depicted in FIG. 7B,identified as Process IV.

[0046] As seen therein, the initial temperature T_(3i)(t) sensed attemperature sensor 30 as a function of time is smoothed, or filtered, inthe manner as previously discussed above, and suitably measured andstored at an initial time t₀. A predetermined rise in temperature ΔT₃ ofthe temperature sensor itself is selected. Power is then supplied attime t₀ to the temperature sensor 30 from a power source 30A connectedthereto to cause its temperature T₃(t) to rise by a predeterminedamount.

[0047] Power may be supplied to the sensor in different ways accordingto the needs of the particular measurement and the relative simplicityor complexity of the required circuitry, three such ways being depictedin FIGS. 8A, 8B, and 8C.

[0048] For example, in a first mode of operation (FIG. 8A), heatingpower may be supplied to the sensor in such a manner as to keep thefinal sensor temperature T_(3f)(t) constant at an initial level ΔT₃above the initial temperature T_(3i)(t₀), i.e. T_(3f)=T_(3i)(t₀)+ΔT₃even when the local blood temperature varies with time, as illustratedin FIG. 9A. Under such conditions, the sensor is maintained at atime-varying temperature increment ΔT₃(t) above the instantaneous localblood temperature, T_(b)(t).

[0049] Alternatively, in a second mode of operation, power can besupplied to the sensor so as to continuously maintain the sensor at afixed temperature increment above the time varying local bloodtemperature, as illustrated in FIG. 9B. Under such conditions,ΔT₃(t)=ΔT₃, a constant, and the sensor temperature varies according toT_(3f)(t)=ΔT₃+T_(3i)(t).

[0050] A third mode of heating may also be convenient when thetemperature sensors are temperature-sensitive resistors, or thermistors.Thus, when a thermistor is used, it may be more convenient to design anelectrical heating circuit that maintains the sensor at a constantresistance increment above the resistance of the sensor that correspondsto the local blood temperature. If R is the corresponding resistance fora sensor temperature T, then these conditions are represented byΔR₃(t)=ΔR₃, a constant, and the sensor resistance varies according toR_(3f)(t)=ΔR₃+R_(3i)(t), as illustrated in FIG. 9C. The change intemperature ΔT₃(t) is then replaced by the change in resistance R₃(t) inthe ratio which is integrated over a cardiac cycle. Further details andexemplary apparatus for such modes of operation are presented anddescribed in U.S. Pat. No. 4,059,982, issued to H. F. Bowman on Nov. 29,1977. With all three of the above approaches, power (P) is supplied toproduce a temperature rise (ΔT) both of which are then related to theinstantaneous blood velocity and, hence, blood flow.

[0051] Techniques in which sensor heating power and temperature can bemeasured and used to provide more detailed information on cardiac outputare described below. The technique involved can be applied to measureboth instantaneous cardiac output, and the cardiac output for anindividual cardiac cycle. Such detailed measurement information greatlyenhances the diagnostic capability of a physician.

[0052] First, a method is described to measure instantaneous volumetricflow (which flow if measured at the location described above is thecardiac output). For each of the particular implementations describedabove, the power P₃(t) applied to the temperature sensor 30 iscontrolled so as to maintain the final temperature of the sensor at adesired value T_(3f). The power applied to the temperature sensor 30 or,more generally, the ratio of the power applied to the sensor to thetemperature increment, P₃(t)/ΔT₃(t), is directly correlated with thefluid and flow properties of the flowing liquid about the sensor.

[0053] For example, the relationship between required sensor power andlocal fluid velocity, V(t), is given by a correlation of the form:

P(t)=4πkaΔT( t) [1÷C ₁ P_(r) ^(n) (2ap V(t)/μ)^(m)]

[0054] Where

[0055] P(t)=instantaneous power to sensor

[0056] k=thermal conductivity of fluid

[0057] a=sensor radius

[0058] ΔT(t)=instantaneous temperature difference between heated sensorand unheated fluid temperature.

[0059] C₁=constant of calibration

[0060] P₅=a non-dimensional “Prandtl” number which relates to theviscosity μ, heat capacity Cp and thermal conductivity k of a fluid.

[0061] n,m=power factors which are determined from experimental data

[0062] p=fluid density

[0063] μ=viscosity

[0064] V(t)=instantaneous fluid velocity

[0065] The fluid flow velocity in the vicinity of the sensor can bedetermined from the required sensor heating power. Volumetric flow inthe vessel can then be determined with one further assumption for thedistribution of the fluid flow within the vessel. For example, assuminga uniform velocity profile within the vessel, volumetric flow F₃ isgiven by

F₃=V A

[0066] where V is the fluid velocity in the vessel and A is the flowarea. If the fluid flow area A is not previously known, it may beinferred from the measurement of average volumetric flow in the vessel.Such average volumetric flow can be determined, for example, by usingthe techniques of the invention already described above herein or byusing other techniques for yielding comparable information. For example,if F is the average cardiac output, typically measured over severalcardiac cycles, as described above, and V is the average fluid velocity,determined by calculating an average value for the instantaneous flowvelocity over at least one cardiac cycle, then one such estimate for theaverage flow area A is given by

{overscore (A)}={overscore (F)}/{overscore (V)}

[0067] Therefore, given the sensor measured heating power, first thefluid velocity and then volumetric flow can be calculated at any desiredinstant in time, i.e., F_(3(t)=)V(E){overscore (A)}, yielding aninstantaneous measure of volumetric flow, i.e., cardiac output.

[0068] In another embodiment, a method to measure cardiac output over asingle cardiac cycle is described. As described above in differentimplementations, the power P₃(t) applied to the temperature sensor 30 iscontrolled so as to maintain the temperature of the sensor at a desiredsignal value T_(3f). The power applied to the temperature sensor 30, ormore generally, as discussed above, the ratio of the power applied tothe sensor to the temperature increment, i.e., P₃(t)/ΔT₃(t), is directlycorrelated with the properties of the fluid flow in the vicinity of thesensor. Thus, the integrated value of the power to temperature ratioover a single cardiac cycle is directly correlated with, i.e., isproportional to the average cardiac output over the cardiac cycle,${\int_{{cardiac}\quad {cycle}}^{\quad}{\frac{P_{3}(t)}{\Delta \quad {T_{3}(t)}}\quad {t}}} \propto \overset{\_}{F}$

[0069] or, alternatively expressed${\frac{1}{T}{\int_{{cardiac}\quad {cycle}}^{\quad}{\frac{P_{3}(t)}{\Delta \quad {T_{3}(t)}}\quad {t}}}} \propto \overset{\_}{F}$

[0070] where T represents the period of the cardiac cycle and {overscore(F)} correspondingly represents cardiac output averaged over the cardiaccycle. Thus, the average cardiac output {overscore (F)} over anindividual cardiac cycle then can be determined from the measured andintegrated power and temperature signals from the sensor.

[0071] Furthermore, an explicit correlation for integrated power andaverage cardiac output over the cardiac cycle may be dispensed with if asimple qualitative indication of the change in cardiac output on acardiac cycle-to-cardiac cycle basis is desired. To obtain suchinformation, a given measurement of cardiac output is taken asassociated with a corresponding measured value of the integrated sensorsignal over a cardiac cycle. The measurement of cardiac output could beobtained intermittently by the techniques described in this invention orother similar techniques. Since cardiac output is known to be correlatedwith the value of the integrated sensor signal over the cardiac cycle,any changes in the sensor signal indicate a corresponding change incardiac output.

[0072] In certain situations, it may be desirable to compensate fortemperature variations in the blood which is flowing past the sensor, asthis may affect the value of F(t). A process for such compensation isdepicted as Process IV in FIG. 7B wherein a temperature T₂(t) is sensedby a second sensor (which may be, for example, sensor 19 or sensor 20)at a location remote from sensor 30 (see FIG. 7A). For example,knowledge of the instantaneous blood temperature is required for theprocess in which the heated sensor is maintained at a constant incrementabove the local blood temperature. In this case, the temperature T₂(t)is used as a proxy for the temperature T₃(t) which would be measured inthe absence of sensor heating.

[0073] In a further alternative embodiment, where only two sensors 19and 20 are utilized (as shown in FIG. 2), sensor 20 can be used as theprimary sensor when calculating instantaneous cardiac output (equivalentto sensor 20 in FIG. 7A) and sensor 19 can be used as the secondarytemperature compensation sensor. In such an embodiment, the averagedcardiac output can be determined using sensors 19 and 20, as set forthin FIGS. 3-6 and the instantaneous cardiac output can then subsequentlybe determined using sensors 19 and 20, as set forth in FIGS. 7B andeither FIGS. 8A, 8B or 8C, such average and instantaneous cardiac outputdeterminations being made in sequence by the microprocessor to providethe cardiac information in both forms, as desired.

[0074] As mentioned above, when using the above described catheter, thevarious flow values which are determined in accordance with theprocesses as discussed above are proportional to flow but may not beequal to the actual flow values unless they are suitably calibratedsince the correspondence between the calculated and actual valuesdepends on the manner in which a particular catheter is constructed andused. A calibration constant for a particular catheter can berepresented by the slope and intercept of a curve which relates thecalculated flow and the actual flow, in accordance with the followingrelationship:

F _(actual) =aF _(calc.) +b

[0075] where, as illustrated in FIG. 10, “a” is the slope of a straightline 35 and “b” is the intercept thereof along the vertical axis. Curve35 can be obtained by using a known catheter and known flow valuestherein to construct a curve 36. The best straight line fit isdetermined as line 35. The slope “a” and intercept “b” are therebydetermined. Such determined values for “a” and “b” can be used with thecalculated flow values in each case to determine the actual flow fromthe calculated flow.

[0076] While the above description discusses preferred embodiments ofthe invention, modifications thereof may occur to those in the artwithin the spirit and scope of the invention. Hence, the invention isnot to be construed as limited to particular embodiments described,except as defined by the appended claims.

What is claimed is:
 1. A method for determining blood flow in a livingbody comprising the steps of: changing the thermal energy level by apredetermined amount at a site in a blood flow path of said living body;detecting the temperatures at a first location upstream of said site anda second location downstream of said site; determining the temperaturedifference between said first and second locations at one energy level;determining the temperature difference between said first and secondlocations at a changed energy level; and calculating blood flow as afunction of the change in energy level and of the temperaturedifferences measured prior to and following the change in energy level.2. A method in accordance with claim 1 wherein said first location issubstantially thermally isolated from thermal energy changes occurringat said site.
 3. A method in accordance with claim 2 wherein said bloodflow path includes at least a portion of the heart of a living body andthe blood flow represents cardiac output.
 4. A method in accordance withclaim 3 wherein said site is at least partially in the right atrium ofthe heart, said first location is in the vena cava of the heart, and thesecond location is in or near the pulmonary artery of the heart.
 5. Amethod in accordance with claim 3 wherein said site is at leastpartially the right atrium of the heart, said first location is in thevena cava of the heart, and the second location is in or near the rightventricle of the heart.
 6. A method in accordance with claims 1, 2, 3,4, or 5 wherein said thermal energy is changed by applying thermalenergy from a catheter borne thermal energy source which is positionedin the blood flow path and wherein temperatures are detected bytemperature sensors in said catheter at said first and second locations,respectively.
 7. A method for determining blood flow in a living bodycomprising the steps of: changing the thermal energy at a site in ablood flow path of said living body, from a first level to a secondlevel; determining a characteristic of the temperature differencebetween the temperatures in said blood flow path at a first locationupstream of said site and at a second location downstream of said siteat said first level; determining a characteristic of the temperaturedifference between the temperatures in said blood flow path at the firstlocation and at the second location at said second level; determiningthe difference between the characteristics of said temperaturedifferences; calculating blood flow as a function of the differencebetween the characteristics of said temperature differences and thechange in thermal energy from said first level to said second level. 8.A method in accordance with claim 7 wherein each of said characteristicsis determined over a specified time period.
 9. A method in accordancewith claim 8 wherein each of said characteristics is the average of thetemperature differences.
 10. A method in accordance with claim 8 whereinthe specified time period is at least one respiratory cycle.
 11. Amethod in accordance with claim 7, 8, 9, or 10 wherein said blood flowpath includes at least a portion of the heart of a living body where theblood flow represents cardiac output.
 12. A method in accordance withclaim 11 wherein said site is at least partially in the right atrium ofthe heart, said first location is in the vena cava of the heart, and thesecond location is in or near the pulmonary artery of the heart.
 13. Amethod in accordance with claim 11 wherein said site is at leastpartially in the right atrium of the heart, said first location is inthe vena cava of the heart, and the second location is in or near theright ventricle of the heart.
 14. A method in accordance with claim 7wherein each of said characteristic temperature difference determiningsteps includes the steps of: detecting temperatures at said firstlocation upstream of said site and at said second location downstream ofsaid site during each cycle of one or more respiratory cycles, when saidthermal energy is at said first level and when said thermal energy is atsaid second level; determining temperature differences between saidtemperatures for each respiratory cycle, when said thermal energy is atsaid first level and when said thermal energy is at said second level;and determining the average of said temperature differences overmultiple respiratory cycles.
 15. A method in accordance with claim 7wherein: said thermal energy level changing step includes applying apredetermined amount of power P at said site to change said thermalenergy level from said first level to said second level and said cardiacoutput calculating step includes the steps of calculating a rise-timecardiac output component as a function of the power P, the calculatedaverage rise-time temperature difference, and the heat capacity ofblood; calculating a fall-time cardiac output component as a function ofthe power P, the calculated fall-time difference, and the heat capacityof blood; and calculating the cardiac output as a function of therise-time and fall-time cardiac components.
 16. A method in accordancewith claims 7, 8, 9, 10 and 15 wherein the steps therein can besuccessively repeated a plurality of times to provide repeatedcalculations of the cardiac output to provide an effectively continuouscalculation thereof.
 17. A method in accordance with claim 16 whereinthe repeated calculations of the cardiac output can be averaged over aselected number of said plurality of times to provide an averagedcardiac output over said selected number of times.
 18. A system fordetermining blood flow in a living body comprising: means for changingthe thermal energy level by a predetermined amount at a site in a bloodflow path of said living body; means for detecting the temperatures at afirst location upstream of said site and a second location downstream ofsaid site; means for determining the temperature difference between saidfirst and second locations at one energy level; means for determiningthe temperature difference between said first and second locations at achanged energy level; and means for calculating blood flow as a functionof the change in energy level and of the temperature differencesmeasured prior to and following the change in energy level.
 19. A systemin accordance with claim 18 wherein said first location is substantiallythermally isolated from thermal energy changes occurring at said site.20. A system in accordance with claim 19 wherein said blood flow pathincludes at least a portion of the heart of a living body and the bloodflow represents cardiac output.
 21. A system in accordance with claim 20wherein said site is at least partially in the right atrium of theheart, said first location is in the vena cava of the heart, and thesecond location is in or near the pulmonary artery of the heart.
 22. Asystem in accordance with claim 20 wherein said site is at leastpartially the right atrium of the heart, said first location is in thevena cava of the heart, and the second location is in or near the rightventricle of the heart.
 23. A system in accordance with claims 18, 19,20, 21 or 22 wherein said system includes a catheter, said thermalenergy changing means is a thermal energy source carried by saidcatheter and positioned in the blood flow path, and said temperaturedetecting means are temperature sensors positioned in said catheter sothat when said catheter is positioned in said blood flow path saidthermal energy source is at said site and said temperature sensors areat said first and second locations, respectively.
 24. A system fordetermining blood flow in a living body comprising: means for changingthe thermal energy at a site in a blood flow path of said living body,from a first level to a second level; means for determining acharacteristic of the temperature difference between the temperatures insaid blood flow path at a first location upstream of said site and at asecond location downstream of said site at said first level; means fordetermining a characteristic of the temperature difference between thetemperatures in said blood flow path at the first location and at thesecond location at said second level; means for determining thedifference between the characteristics of said temperature differences;means for calculating blood flow as a function of the difference betweenthe characteristics of said temperature differences and the change inthermal energy from said first level to said second level.
 25. A systemin accordance with claim 24 wherein said characteristic determiningmeans determines said characteristics over a specified time period. 26.A system in accordance with claim 25 wherein each of saidcharacteristics is the average of the temperature differences.
 27. Asystem in accordance with claim 25 wherein the specified time period isat least one respiratory cycle.
 28. A system in accordance with claims24, 25, 26 or 27 wherein said blood flow path includes at least aportion of the heart of a living body where the blood flow representscardiac output.
 29. A system in accordance with claim 20 wherein saidsite is at least partially in the right atrium of the heart, said firstlocation is in the vena cava of the heart, and the second location is inor near the pulmonary artery of the heart.
 30. A system in accordancewith claim 28 wherein said site is at least partially in the rightatrium of the heart, said first location is in the vena cava of theheart, and the second location is in or near the right ventricle of theheart.
 31. A system in accordance with claim 24 wherein each of saidcharacteristic temperature difference determining means includes: meansfor detecting temperatures at said first location upstream of said siteand at said second location downstream of said site during each cycle ofone or more respiratory cycles, when said thermal energy is at saidfirst level and when said thermal energy is at said second level; meansfor determining temperature differences between said temperatures foreach respiratory cycle, when said thermal energy is at said first leveland when said thermal energy is at said second level; and means fordetermining the average of said temperature differences over multiplerespiratory cycles.
 32. A method in accordance with claim 24 wherein:said thermal energy level changing means includes means for applying apredetermined amount of power P at said site to change said thermalenergy level from said first level to said second level; and saidcardiac output calculating means includes means for calculating arise-time cardiac output component as a function of the power P, thecalculated average rise-time temperature difference, and the heatcapacity of blood; means for calculating a fall-time cardiac outputcomponent as a function of the power P, the calculated fall-timedifference, and the heat capacity of blood; and means for calculatingthe cardiac output as a function of the rise-time and fall-time cardiaccomponents.
 33. A system in accordance with claims 24, 25, 26 or 27wherein said system calculates the cardiac output repeatedly to providean effectively continuous calculation thereof.
 34. A system inaccordance with claim 33 and further including means responsive to therepeated calculations of the cardiac output can for averaging saidcalculation over a selected number of repeated calculations to providean averaged cardiac output over said selected number of calculations.35. A method for determining blood flow in a living body comprising thesteps of: changing the value of the selected parameter of blood at asite in a blood flow path of said living body, from a first level to asecond level; determining the difference between the value of theselected parameter in said blood flow path at a first location upstreamof said site and at a second location downstream of said site at saidfirst level; determining the difference between the value of theselected parameter in said blood flow path at the first location and atthe second location at said second level; determining the differencebetween the value obtained in the first said difference determiningsteps and the value obtained in the second said difference determiningsteps; and calculating blood flow as a function of the differencebetween the values obtained in said first and second differencedetermining steps and the change in the value of the selected parameterfrom said first level to said second level.
 36. A method in accordancewith claim 35 wherein said blood flow path includes at least a portionof the heart of a living body where the blood flow represents cardiacoutput.
 37. A system for determining blood flow in a living bodycomprising: means for changing the value of the selected parameter ofblood at a site in a blood flow path of said living body, from a firstlevel to a second level; means for determining the difference betweenthe value of the selected parameter in said blood flow path at a firstlocation upstream of said site and at a second location downstream ofsaid site at said first level; means for determining the differencebetween the value of the selected parameter in said blood flow path at afirst location upstream of said site and at a second location downstreamof said site at said first level; means for determining the differencebetween the value of the selected parameter in said blood flow path atthe first location and at the second location at said second level;means for determining the difference between the value obtained in thefirst said difference determining steps and the value obtained in thesecond said difference determining steps; and means for calculatingblood flow as a function of the difference between the values obtainedin said first and second difference determining steps and the change inthe value of the selected parameter from said first level to said secondlevel.
 38. A system in accordance with claim 37 wherein said blood flowpath includes at least a portion of the heart of a living body where theblood flow represents cardiac output.
 39. A method for determininginstantaneous blood flow in a living body comprising the steps of:determining the temperature level at a selected location in a blood flowpath of said living body; heating said selected location in said bloodflow path to a final temperature level; determining the finaltemperature level; determining the ratio of the heating power requiredto heat said selected location to said final temperature level to thechange in temperature level at said selected location.
 40. A method inaccordance with claim 39 wherein said indicating step includesintegrating said ratio over a single cardiac cycle and dividing theintegrated value by the period of said cardiac cycle to obtain theaverage instantaneous blood flow in said living body over said cardiaccycle.
 41. A method in accordance with claims 39 or 40 wherein saidheating and said final temperature level determining steps includedetermining the initial temperature level at said selected locationbefore heating said selected location; heating said selected location tosaid final temperature level; maintaining said final temperature levelat a constant value while heating said selected location over time; anddetermining the time varying change in the temperature level at saidselected location which is required to maintain said final temperaturelevel at said constant value.
 42. A method in accordance with claims 39or 40 wherein said heating and said final temperature level determiningsteps include heating said selected location from an initial temperaturelevel to a final temperature level by changing the temperature level bya fixed amount; and maintaining the changing temperature level at saidfixed amount over time and determining the time varying temperaturelevel over said time.
 43. A method in accordance with claims 39 or 40wherein said heating step includes heating a sensor positioned at saidselected location, said sensor having a resistance R which varies as afunction of the temperature thereof and further including the steps of:heating said sensor to a final resistance value thereby changing theresistance value of said sensor; maintaining the changing resistancevalue of said sensor during heating at a fixed amount over time; anddetermining the time varying final resistance value of said sensorduring the heating over said time; and further wherein said ratiodetermining step includes determining the ratio of the heating powerrequired to heat said sensor to said final resistance value to the fixedchanging resistance value thereof.
 44. A device for insertion into thebloodstream of a living organism to obtain physiological datacomprising: an elongated flexible catheter adapted to be inserted intothe venous or arterial system of the living organism; first temperaturesensing means carried by said catheter; second temperature sensing meanscarried by said catheter positioned to be upstream of said firsttemperature sensing means when in use; and heating means carried by saidcatheter between said first and second temperature sensing means andpositioned to be substantially thermally isolated from said secondtemperature sensing means when in use; said first and second temperaturesensing means and said heating means being adapted to be incommunication with a data processing system.
 45. A device in accordancewith claim 44 and further comprising thermistor means carried by saidcatheter and positioned to be downstream of said heating means when inuse, said thermistor means being adapted to be in communication withsaid data processing system.
 46. A device for insertion into thebloodstream of a living organism to obtain physiological datacomprising: an elongated flexible catheter adapted to be inserted intothe venous or arterial system of the living organism; temperaturesensing means carried by said catheter; and thermistor means carried bysaid catheter and positioned to be downstream of said temperaturesensing means when in use; said temperature sensing means and saidthermistor means being adapted to be in communication with a dataprocessing system.